Adult Dosing

Vulvar and vaginal atrophy associated with menopause (Estrace)

Cream

• Usual dose: 2-4 g PV qd x 1-2 weeks, then gradually reduce to one half of initial dose x 1-2 weeks
• Maintenance dose: 1 g PV 1-3 times weekly

• Start with the lowest effective dose and for the shortest duration consistent with individual treatment goals
• Re-evaluate periodically as clinically appropriate to determine if treatment is to be continued

Moderate to severe vulvar/vaginal atrophy and vasomotor symptoms associated with menopause (Estring, Femring)

Ring

• 1 vaginal ring q3 months

• Start with the lowest effective dose and for the shortest duration consistent with individual treatment goals
• Insert the ring as deeply as possible into the upper one-third of the vaginal vault. The ring is to remain in place continuously for 3 months, after which it is to be removed and, if appropriate, replaced by a new ring
• Exact position is not critical to function. When ring is in place, patient should not feel anything. If patient feels discomfort, ring should be pushed gently further into the vagina
• If the ring falls out at any time during the 3-month treatment period, it should be rinsed in lukewarm water and re-inserted by the patient
• Re-evaluate periodically as clinically appropriate to determine if treatment is to be continued

Moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause (Vagifem)

Tabs

• 10 mcg PV qd x 2 wks
• Maintenance dose: 10 mcg twice weekly

• Start with the lowest effective dose and for the shortest duration consistent with individual treatment goals
• Re-evaluate periodically as clinically appropriate to determine if treatment is to be continued

Pediatric Dosing

• Not indicated

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of atrophic vaginitis and vulvar atrophy associated with menopause (Estrace)
• Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause (Estring, Femring, Vagifem)
• Treatment of moderate to severe vasomotor symptoms associated with menopause (Estring, Femring)

• Hypersensitivity to any of the ingredients of the product
• Undiagnosed abnormal genital bleeding
• Known, suspected, or history of breast cancer
• Known or suspected estrogen-dependent neoplasia
• Active or history of deep vein thrombosis
• Active or history of pulmonary embolism
• Active or recent (within the past year) arterial thromboembolic disease (such as stroke and MI)
• Known liver dysfunction or disease
• Known or suspected pregnancy
• Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

• Use of unopposed estrogens increases the risk of endometrial cancer in a woman with a uterus. Adding a progestin to estrogen therapy significantly reduces the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Closely monitor all women taking estrogen therapy. Use adequate diagnostic measures such as endometrial sampling to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal genital bleeding
• Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia. According to the estrogen-alone substudy conducted by the Women's Health Initiative (WHI), use of daily oral conjugated estrogens (CE) caused increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment, relative to placebo. The Women's Health Initiative Memory Study (WHIMS) estrogen-alone ancillary study of the WHI reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo. It is not known whether this finding applies to younger postmenopausal women. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens. Use the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman

Renal Dose Adjustment

• Renal impairment: Dose adjustments not defined

Hepatic Dose Adjustment

• Hepatic impairment: Contraindicated

• Estrogen-alone and estrogen plus progestin therapy may cause an increased risk of cardiovascular events such as DVT, pulmonary embolism, stroke, and myocardial infarction; discontinue the drug immediately if any of these events occur or be suspected [US Black Box warning]
• Use of unopposed estrogens in a woman with intact uterus increases the risk of endometrial cancer [US Black Box warning]
• Estrogen plus progestin therapy in postmenopausal women may increase the risk of breast cancer. Perform routine breast examinations; schedule mammograms based on patient age, risk factors, and prior mammogram results
• Estrogen-alone and estrogen plus progestin therapy may increase the risk of dementia in postmenopausal women 65 years of age and older [US Black Box warning]
• A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery has been reported in postmenopausal women receiving estrogen therapy
• Estrogen therapy may cause severe hypercalcemia in women with breast cancer and bone metastases. Discontinue therapy if hypercalcemia occurs and initiate appropriate measures to reduce the serum calcium level
• Incidences of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy; consider adding progestins to estrogen therapy in such patients
• Retinal vascular thrombosis has been reported in women receiving estrogens. Discontinue therapy pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia or migraine. Permanently discontinue therapy if examination reveals papilledema or retinal vascular lesions
• Estrogen use may cause substantial increases in blood pressure; monitor BP at regular intervals during therapy
• Use of progestin with estrogen in a continuous regimen has been reported to lower the incidence of endometrial hyperplasia than would be induced by estrogen-alone therapy. However, there is a possible increased risk of breast cancer associated with the use of progestins with estrogens compared to estrogen-alone regimens
• Estrogen therapy may be associated with elevations of plasma triglycerides in patients with preexisting hypertriglyceridemia, leading to pancreatitis; discontinue therapy if pancreatitis develops
• Estrogens may be poorly metabolized in women with hepatic impairment. Use cautiously in women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy; discontinue the drug in case of recurrence
• Estrogen administration may cause increased thyroid-binding globulin (TBG) levels. Women on thyroid hormone replacement therapy also receiving estrogens may require increased doses of their thyroid replacement therapy. Monitor thyroid function regularly to maintain free thyroid hormone levels in an acceptable range
• Estrogens may cause fluid retention; use cautiously in patients with cardiac or renal dysfunction
• Use cautiously in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur
• Therapy may cause an exacerbation of asthma, diabetes mellitus, migraine, epilepsy, porphyria, hepatic hemangiomas and systemic lupus erythematosus; use with caution in women with these conditions
• Use of estrogen-alone therapy for 10 or more years may increase the risk of ovarian cancer
• Incidences of local abrasion caused by the Vagifem applicator have occurred in women with severely atrophic vaginal mucosa
• Vaginal ring may not be suitable for women with conditions that make vagina more prone to vaginal irritation or ulceration, or make expulsions more likely, including narrow vagina, vaginal infection or stenosis, rectoceles, cervical prolapse, and cystoceles
• Vaginal infections should be treated with appropriate antimicrobial therapy before initiation of therapy with vaginal ring
• Topical vaginal products should be considered when prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy

Cautions: Use cautiously in

• Cardiovascular diseases
• Cardiac disease risk
• Hypothyroidism
• Chorea
• Surgery or prolonged immobilization
• Endometriosis
• Obesity
• Patients >65 yrs
• Tobacco use

Pregnancy Category:X

Breastfeeding: Limited data on the use of estradiol during breastfeeding indicates that the amount transferred into breastmilk is significantly influenced by the route of administration and dosage forms. Vaginal administration results in measurable amounts in milk. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 18 July 2011). As per manufacturer's data, estrogen administration to nursing mothers interferes with lactation by decreasing the quantity and quality of the breast milk. Detectable amounts are secreted in breast milk, hence should not be used during lactation.

• CNS: Headache, aggravated migraine, dizziness, mental depression, chorea exacerbation, nervousness, mood disturbances, irritability, insomnia, exacerbation of epilepsy, dementia
• GU: Intermenstrual bleeding, vaginal candidiasis, vulvovaginitis, uterine pain, uterine fibroid enlargement, UTI, vaginal discharge, vaginal irritation, vaginal ulceration/erosion (vaginal ring form), breast tenderness/enlargement/pain, nipple discharge, genital disorder female, genital moniliasis, changes in vaginal bleeding pattern, abnormal withdrawal bleeding/flow, dysmenorrhea, vaginitis, change in amount of cervical secretion, libido changes, changes in cervical ectropion, ovarian cancer, endometrial hyperplasia, endometrial cancer, galactorrhea, fibrocystic breast changes, breast cancer, ovarian CA
• CV: MI, stroke, hypertension, edema, deep and superficial venous thrombosis, thrombophlebitis, pulmonary embolism
• RESP: URTI, exacerbation of asthma
• GI: Abdominal distension, nausea, vomiting, abdominal cramps, bloating, cholestatic jaundice, increased incidence of gallbladder disease, pancreatitis, enlargement of hepatic hemangiomas, ischemic colitis, intestinal obstruction
• DERM: Chloasma or melasma, erythema multiforme, erythema nodosum, hemorrhagic eruption, loss of scalp hair, hirsutism, genital pruritus, rash, urticaria, SLE exacerbation
• METABOLIC: Increase or decrease in weight, hypocalcemia, reduced carbohydrate tolerance, increased triglycerides
• HEMA: Aggravation of porphyria
• EENT: Sinusitis, nasopharyngitis, retinal vascular thrombosis, intolerance to contact lenses
• MUSC: Arthralgia, arthritis, back pain, pain in limb, leg cramps
• LOCAL: Application site reactions
• HYPERSENSITIVITY: Hypersensitivity, anaphylaxis/anaphylactoid reactions
• MISC: Edema, fluid retention, flu-like symptoms, hot flushes, toxic shock syndrome (vaginal ring form)

• Estrogens; responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Through a negative feedback mechanism, circulating estrogens regulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) and act to reduce the elevated levels of these hormones in postmenopausal women
• Metabolized by liver; CYP450: 3A4 substrate, also undergoes enterohepatic recirculation
• Estradiol is reversibly converted to active metabolite estrone, and both can be converted to estriol, which is the major urinary metabolite
• Renally excreted as conjugates
• Half-life: Unknown

US Trade Name(s)

• Estrace
• Estring
• Femring
• Vagifem

US Availability

Estrace

• CRE: 0.01%

Estring

• RING: 0.0075 mg/24 hr

Femring (estradiol acetate)

• RING: 0.05 mg/24 hr
• RING: 0.1 mg/24 hr

Vagifem

• TABS: 10 mcg

Canadian Trade Name(s)

• Estring
• Vagifem

Canadian Availability

Estring

• RING: 0.0075 mg/24 hr

Vagifem

• ETABS: 10, 25 mcg

UK Trade Name(s)

• Estring
• Vagifem

UK Availability

Estring

• RING: 0.0075 mg/24 hr

Vagifem

• ETABS: 10, 25 mcg

Australian Trade Name(s)

• Vagifem

Australian Availability

Vagifem

• PESSARY: 25 mcg

[Outline]

Endocrine/Metabolic

Sex Hormones

Estrogens

Obstetrics/Gynecology

Sex Hormones

Estrogens

Pricing data from www.DrugStore.com in U.S.A.

• Femring 0.05 MG/24HR RING [Box] (WARNER CHILCOTT PROF PROD DIV)
  1 24hr = $202.99
  3 24hr = $590.95
• Estrace 0.1 MG/GM CREA [Tube] (WARNER CHILCOTT PROF PROD DIV)
  42.5 gm = $135.99
  127.5 gm = $389.98
• Estring 2 MG RING [Box] (PFIZER U.S.)
  1 mg = $215.98
  3 mg = $613.96
• Femring 0.1 MG/24HR RING [Box] (WARNER CHILCOTT PROF PROD DIV)
  1 24hr = $237.98
  3 24hr = $698.98
• Vagifem 10 MCG TABS [Box] (NOVO NORDISK)
  18 mcg = $144.98
  54 mcg = $409.98
• Vagifem 10 MCG TABS [Box] (NOVO NORDISK)
  8 mcg = $69.99
  24 mcg = $190.96

Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.

Drug Name: Vagifem 0.01 MG Vaginal Tablet

Ingredient(s): Estradiol

Imprint: N/A

Color(s): White

Shape: Round

Size (mm): 6.00

Score: 1

Inactive Ingredient(s): N/A

Drug Label Author:
Novo Nordisk

DEA Schedule:
Non-Scheduled

Drug Name: Vagifem 0.025 MG Vaginal Tablet

Ingredient(s): Estradiol

Imprint: N/A

Color(s): White

Shape: Round

Size (mm): 6.00

Score: 1

Inactive Ingredient(s): N/A

Drug Label Author:
Novo Nordisk

DEA Schedule:
Non-Scheduled